Synthesis, Characterization, and Biological Data for Potential Anticancer Gold(III) Complexes. Open Access

Hudson, Zachary Derek (2010)

Permanent URL: https://etd.library.emory.edu/concern/etds/dr26xx55s?locale=en
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Abstract

Abstract

Synthesis, Characterization, and Biological Data for Potential Anticancer Gold(III)
Complexes.

By Zachary D. Hudson

In an effort to discover potential alternatives to the anti-cancer drug cisplatin, the
synthesis of gold(III) polypyridyl coordination complexes was pursued. Specifically, this
report describes the synthesis and characterization of a series of 2,9-dialkyl-1,10-
phenanthroline gold(III) coordination complexes (R = n-butyl, sec-butyl, and tert-butyl),
along with preliminary biological data. Due to the steric hindrance imparted by the alkyl
subsitutents, these ligands do not react with HAuCl4 to form square-planar gold(III)
dichloride complex ions, as is the case with 1,10-phenanthroline, but instead form salts
comprised of [AuCl4]- anions and protonated 2,9-dialkylphenanthroline cations
(compounds 1 and 2). In an effort to facilitate direct binding between the substituted
phenanthroline and the gold(III) metal center, reactions were carried out between the
ligand and NaAuCl4 in the presence of a Ag(I) salt. The precipitation of one equivalent of
AgCl afforded the formation of neutral, distorted square pyramidal gold(III) trichloride
complexes (compounds 3 and 4). Substitutions which are 1° or 2° at the alpha carbon of
the alkyl subsituent allow direct metal-ligand coordination, whereas a 3° substituent
inhibits chelation and results only in the formation of a salt comprised of a protonated
phenanthroline cation and an [AuCl2]- anion (compound 5). Compounds 1- 4 have been
characterized by 1H NMR, UV-Vis, and IR spectroscopy, and X-ray crystallography.
Assays probing cytotoxicity within existing tumor cell lines are reported herein, along
with in vitro inhibition studies of the mitochondrial enzyme thioredoxin reductase.

Table of Contents


Table of Contents

1. Introduction ..............................................................................................................................................9
2. Experimental.............................................................................................................................................6
2.1 General Procedures............................................................................................................................6
2.2 X-ray Crystallography (compounds 1 and 2) .....................................................................................7
2.3 X-ray Crystallography (compounds 3-5) ............................................................................................8
2.4 Synthesis of Compound 1....................................................................................................................9
2.5 Synthesis of Compound 2..................................................................................................................10
2.6 Synthesis Compound 3......................................................................................................................11
2.7 Synthesis of Compound 4..................................................................................................................11
2.8 Synthesis of Compound 5..................................................................................................................12
2.9 Cytotoxicity Assays ...........................................................................................................................12
2.10 Thioredoxin Reductase Assay .........................................................................................................13
3. Results and Discussion ...........................................................................................................................14
3.1 Synthesis and Spectroscopic Characterization .................................................................................14
3.2 X-ray Crystal Structures ...................................................................................................................18
3.3 Thioredoxin Reductase Inhibition and Cytotoxicity Assays..............................................................23
3.4 Stability Data....................................................................................................................................26
4. Conclusions and Future Work ................................................................................................................29
5. References ..............................................................................................................................................31

Tables and Figures
Figure 1 ......................................................................................................................................................9
Figure 2 ......................................................................................................................................................2
Figure 3 ......................................................................................................................................................4
Figure 4 ......................................................................................................................................................6
Figure 5 ......................................................................................................................................................9
Figure 6 ....................................................................................................................................................10
Figure 7 ....................................................................................................................................................15
Figure 8 ....................................................................................................................................................17

Figure 9 ....................................................................................................................................................18
Figure 10 ..................................................................................................................................................19
Figure 11 ..................................................................................................................................................20
Figure 12. .................................................................................................................................................21
Figure 13 ..................................................................................................................................................22
Figure 14 ..................................................................................................................................................24
Figure 15 ..................................................................................................................................................26
Figure 17 ..................................................................................................................................................29
Figure 18 ..................................................................................................................................................31
Scheme 1....................................................................................................................................................6
Scheme 2..................................................................................................................................................28
Table 1 .....................................................................................................................................................23
Table 2 .....................................................................................................................................................25

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